The present invention relates generally to antibodies and, more specifically, to antibodies against interleukin-1 receptors.
Interleukin-1xcex1 and Interleukin-1xcex2 (IL-1xcex1 and IL-1xcex2) are distantly related polypeptide hormones which play a central role in the regulation of immune and inflammatory responses. These two proteins were originally both classified as IL-1, based on a shared lymphocyte activation factor (LAF) activity, and a common major cellular source, activated macrophages. As information has accumulated from studies using purified natural and recombinant IL-1 molecules, it has become clear that IL-1xcex1 and IL-1xcex2 each mediate most, if not all, of the wide range of activities previously ascribed to IL-1. The basis for this nearly identical spectrum of biological activities is thought to be a single class of plasma membrane IL-1 receptors which bind both IL-1xcex1 and IL-1xcex2. The binding of IL-1 to these receptors is specific, and occurs with a high affinity (1xc3x9710xe2x88x9210M).
Polyclonal antibodies have long been utilized for various aspects of research and development, but in 1975 Kxc3x6hler and Milstein discovered a new technique which revolutionized the production and use of antibodies (see Kxc3x6hler and Milstein, Nature 256:495 1975). This technique utilized somatic cell hybridization to generate a continuous xe2x80x9chybridomaxe2x80x9d cell line which produced large quantities of a single specific antibody, also referred to as a monoclonal antibody.
It would be beneficial if such antibodies against the IL-1 receptor were available, as they may be useful for diagnosis and therapy, as well as for various research applications. For example, antibodies may be utilized in clinical applications to diagnose the presence of IL-1 receptor in a patient""s serum, or may be administered therapeutically to bind to and target IL-1 receptor bearing cells for elimination or neutralization. Additionally, antibodies may be utilized in various research applications such as the purification of recombinantly produced IL-1 receptor, or in assays which detect the presence of the IL-1 receptor.
The present invention provides such antibodies and, furthermore, provides other related advantages.
The present invention provides monoclonal antibodies which specifically bind to mammalian IL-1 receptors. Within one embodiment of the invention, the monoclonal antibody is selected from the group consisting of human and mouse monoclonal antibodies. Within selected embodiments, the monoclonal antibody blocks the binding of IL-1 to the IL-1 receptor. Within another embodiment the mammalian IL-1 receptor is selected from the group consisting of murine and human IL-1 receptor. Within a related aspect, a therapeutic composition is provided comprising a monoclonal antibody to the IL-1 receptor as described above and a physiologically acceptable carrier or diluent.
Within another aspect of the present invention, a binding protein is provided which specifically binds to a mammalian IL-1 receptor, which may be, for example, a fragment of an antibody or a fusion protein comprising at least one domain derived from an antibody. Within a related aspect, a therapeutic composition is provided comprising a binding protein which specifically binds to mammalian IL-1 receptor, and a physiologically acceptable carrier or diluent.
Within yet another aspect of the present invention, a method for detecting IL-1 receptors on cells is provided comprising the steps of (a) incubating the cells with a monoclonal antibody, as described above, which is labeled, and (b) detecting the presence of bound antibody. Within another aspect, a method for detecting soluble IL-1 receptor in serum is provided comprising the steps of (a) incubating serum suspected of containing soluble IL-1 receptor with a solid support having monoclonal antibodies as described above affixed thereto under conditions and for a time sufficient for binding to occur, (b) incubating the solid support with a second labeled monoclonal antibody specific for mammalian IL-1 receptors under conditions and for a time sufficient for binding to occur, and (c) detecting the presence of bound labeled antibody.
These and other aspects of the present invention will become evident upon reference to the following detailed description and attached drawings.